Publisher Health

Ribosomal DNA (rDNA) is present in hundreds of copies in the genome, but has not previously been part of genetic analyses. A new study of 500,000 individuals indicates that people who have more copies of rDNA are more likely to develop inflammation and diseases during their lifetimes.
Standard genetic analysis techniques have not studied areas of the human genome that are repetitive, such as ribosomal DNA (rDNA), a fundamental part of the molecular mechanism which makes proteins in cells. A new study, led by Vardhman Rakyan and Francisco Rodriguez-Algarra from Queen Mary University of London’s Blizard Institute in collaboration with David Evans from The University of Queensland’s Institute for Molecular Bioscience, has discovered that genetic disposition to disease can be found in these previously understudied areas of the genome. These results suggest that wider genome analysis could bring opportunities for preventative diagnostics, novel therapeutics, and greater insight into the mechanism of different human diseases.
In this study, co-funded by Barts Charity, Rosetrees Trust, and the Biotechnology and Biological Sciences Research Council (BBSRC), samples from 500,000 individuals in the UK Biobank project were analysed. Researchers used new whole genome sequencing (WGS) techniques to identify differences in numbers of copies of rDNA in each sample, and compared them with other health metrics and medical records.
The researchers found that the number of copies of rDNA in an individual showed strong statistical association with well-established markers of systemic inflammation — such as Neutrophil-to-Lymphocyte ratio (NLR), Platelet-to-Lymphocyte ratio (PLR), and Systemic Immune-Inflammation index (SII). These statistically significant associations were seen in the genomes of individuals of different ethnicities, suggesting a common indicator for risks of future disease.
rDNA copy number was also linked with an individual’s kidney function within the sample of individuals of European ancestry. A similar effect was seen in samples from other ancestries, but further research using larger sample sizes will be needed to confirm this connection.
Professor Vardhman Rakyan, from the Genomics and Child Health in the Blizard Institute at Queen Mary, said: “Our research highlights the importance of analysing the whole genome to better understand the factors impacting on our health. This study is also an example of how having access to large biobanks allows us to make unexpected discoveries, and provides new avenues for harnessing the power of genetics to understand human diseases.”
Professor David Evans, from The University of Queensland’s Institute for Molecular Bioscience, said: “Geneticists have long struggled to fully explain the genetic basis of many common complex traits and diseases. Our work suggests that at least part of this missing heritability resides in difficult to sequence regions of the genome such as those encoding ribosomal copy number variation.”
Victoria King, Director of Funding and Impact at Barts Charity, said: “We’re delighted to have supported this work which could lead to better prevention and treatment for many different diseases. Using samples from UK Biobank participants, this study highlights the exciting potential of examining previously overlooked areas of the genome.”

The protein galectin-1 (Gal-1) has been identified as a new PET imaging biomarker for immune checkpoint blockade (ICB) therapy, allowing physicians to predict the tumor responses before beginning treatment. Information garnered from Gal-1 PET imaging could also be used to facilitate patient stratification and optimize immunotherapy, enabling targeted interventions and improving patient outcomes. This research was published in the May issue of The Journal of Nuclear Medicine.
Immunotherapies, such as ICB, have produced promising clinical outcomes in melanoma, non-small cell lung cancer, and several other types of tumors. However, only a subgroup of patients experiences positive outcomes with objective response rates spanning between five and 60 percent.
“Developing reliable approaches for assessing responses and selecting eligible patients for immunotherapy remains challenging,” said Zhaofei Liu, PhD, Boya Distinguished Professor at Peking University in Beijing, China. “Current clinical criteria for monitoring solid tumor responses to immunotherapy are based on CT and MRI scans, but these methods result in a considerable delay between treatment commencement and response evaluation. Molecular imaging techniques, especially PET, have emerged as robust tools for predicting immunotherapy effectiveness through the real-time, quantitative, and noninvasive assessment of biomarkers in vivo.”
In the study, a mouse model was utilized to identify new imaging biomarkers for tumor responses to ICB therapy. Through a proteomic analysis (separation, identification, and quantification of proteins in a tumor), researchers found that tumors exhibiting low Gal-1 expression responded positively to ICB therapy.
Next, Gal-1 was labeled with 124I and the radiotracer (124I-α-Gal-1) and small animal PET imaging and biodistribution studies were conducted to assess the specificity of the radiotracer. PET imaging with 124I-αGal-1 showed the immunosuppressive status of the tumor microenvironment, thus enabling the prediction of ICB resistance in advance of treatment. For tumors that were not predicted to respond well to ICB therapy, researchers developed a rescue strategy that utilized a Gal-1 inhibitor that significantly improved the chance for success.
“Gal-1 PET opens avenues for the early prediction of ICB efficacy before treatment initiation and facilitates the precision design of combinational regimes,” noted Liu. “This sensitive approach has the potential to achieve individualized precision treatment for patients in the future.”
This research was published online in March 2024.

As people age, they become more prone to blood clotting diseases, when blood cells called platelets clump together when they don’t need to and can cause major issues such as strokes and cardiovascular disease. For decades, scientists have studied why older people’s blood cells behave in this way, using their insights to develop the myriad of blood-thinning drugs now on the market for treating the leading cause of death in the United States.
Now, UC Santa Cruz Professor of Biomolecular Engineering Camilla Forsberg and her research group have discovered a distinct, secondary population of platelets that appears with aging and have hyperreactive behavior and unique molecular properties, which could make them easier to target with medication. The researchers traced this population of platelets to its stem cell origins, finding what they identify as the first-ever-discovered age-specific development pathway from a stem cell to a distinct mature platelet cell.
“The question for decades and decades has been: why are aging people at such high risk for excessive blood clotting, stroke, and cardiovascular disease?” Forsberg said. “We have this discovery of a whole new pathway that progressively appears with aging — troublemakers! That was never part of the discussion.”
The research group presented their findings in a paper published in the  journal Cell. First author Donna Poscablo, Forsberg’s former Ph.D. student who is now a postdoctoral scholar at Stanford University, and her peers carried out these experiments with the resources and training environment at the Institute for the Biology of Stem Cells (IBSC) at UC Santa Cruz.
Understanding platelets
Platelet cells are one of three types of blood cells produced by the body, with red and white blood cells being the other two. Millions of these cells float around in the blood at all times, and when an injury occurs either internally or externally, they clot together to form a natural, living bandaid. Platelet dysregulation, which is known to increase with age, occurs when these cells are either hyperreactive and form clots too often, or are underperforming. In both cases the body can’t properly manage bleeding and clotting, although hyperreactivity is a much more widely-seen problem.
All blood cells begin as hematopoietic stem cells, a special class of stem cells, and then mature through a series of intermediary steps called a “differentiation pathway” that lead them to their fate as either platelets, red blood cells, or white blood cells. It’s been known for decades that these hematopoietic stem cells decline with age, but that presents a contradiction for scientists: if the hematopoietic cells are less healthy, then why are the platelets they create hyperreactive?

A ‘shortcut’ pathway
As stem cell biologists, the researchers at UC Santa Cruz approached this question by investigating the hematopoietic stem cells.
They conducted experiments that allowed them to trace the lineages of these stem cells in mouse models, and discovered that in aged mice some of their platelets did not travel along the differentiation pathway. Instead, they took what the UCSC researchers dubbed a “shortcut” pathway, skipping over the intermediary steps and immediately becoming megakaryocyte progenitors, the blood cell stage immediately before platelet production. To the researchers’ knowledge, this is the first age-specific stem cell pathway ever discovered.
“People think of [platelets and red blood cells] as one lineage that shares regulation and intermediate stages until the very end,” Forsberg said. “To see that [the secondary platelet population] were completely separated all the way from the stem cell level, only in aged mice, was really surprising.”
While the population of platelets produced from the shortcut pathway are hyperreactive, the platelets produced from the main pathway continue to behave like the platelets in a young person.
“The gradual differentiation cascade maintains a youthful property, and I feel like that is also surprising within itself,” Poscablo said.

They found that the hyperreactive secondary platelets start to be produced around midlife for the mice, with their population growing progressively with aging. As of now, the researchers have not found a trigger that begins the production of this secondary pathway. Unexpectedly, however, it does not seem to be triggered by the aging environment itself: when a young hematopoietic stem cell is transferred into an aged environment, it doesn’t seem to trigger the shortcut pathway; and when an aged hematopoietic stem cell is put into young environment, the old stem cells continue to operate as old stem cells.
“That was surprising, the age resilience of the other pathway,” Forsberg said. “One of the platelet populations is not affected at all [by aging], whereas the one we have discovered is — so the whole phenomenon is not primarily induced by the environment, but by the differentiation path.”
Choosing better treatments
Knowing that this secondary population of platelets exists will help researchers find new ways to target and regulate these problematic cells via their stem cells. Before this, researchers have not tried to target these upstream cells.
“From our expertise, we can ask the questions of how to target the hematopoietic stem cell and now the megakaryocyte progenitor, which has never really been highlighted before as a place to target,” Poscablo said.
Targeting these cells may not require the creation of new medications, but more simply inform the prescription of existing blood thinners such as Aspirin, which treat different patients to varying degrees even if they present with similar clotting-related symptoms. Using their mouse models, the researchers will identify which of the two populations of stem cells are more sensitive to Aspirin and the myriad of other platelet drugs on the market.
The UCSC researchers are also currently working on finding this secondary population of platelets in human cells with the support of a grant from the California Institute for Regenerative Medicine (CIRM). In the mouse models, they will continue to study how to manipulate and control the shortcut pathway, with funding from the National Institutes of Health (NIH) .
Collaborators on this research included UCSC Assistant Professor of Applied Mathematics Vanessa Jönsson and University of Michigan Medical School’s Reheman Adili and Michael Holinstat. Current and former IBSC scholars on this project included Atesh Worthington (now at UC San Francisco), Stephanie Smith-Berdan, Marcel Rommel, Bryce Manso, Lydia Mok, Roman Reggiardo, Taylor Cool, Raana Mogharrab, Jenna Myers, Steven Dahmen, Paloma Medina, Anna Beaudin (now at the University of Utah, Salt Lake City), and Scott Boyer.

Three out of four U.S. adults support the use of emerging technologies that estimate a future child’s likelihood of developing health conditions influenced by multiple genes — such as diabetes, heart disease, and depression — before an embryo is implanted during in vitro fertilization (IVF), according to a new public opinion survey led by researchers at Harvard Medical School.
Results of the survey, to be published May 14 in JAMA Network Open, underscore the need for public education and conversation about the positive and negative implications of these ethically fraught technologies, the researchers said.
Although the approach, known as polygenic embryo screening, is not yet available in most IVF clinics, a few companies have begun offering such estimates — or risk scores — to gauge disease risk, the researchers noted.
“Polygenic embryo screening is largely unregulated in the United States, and without proper context and focused patient education, risk scores can create false expectations,” said first author Rémy Furrer, research fellow in bioethics in the Department of Global Health and Social Medicine in the Blavatnik Institute at HMS.
“This survey rings the alarm that geneticists, behavioral scientists, bioethicists, clinicians, and genetic counselors need to work together to figure out ways to communicate the limitations to people, so they understand what polygenic risk scores do and don’t provide,” he said.
Nearly three-quarters of respondents said they support using such screening to assess the risk of a future child developing a physical or psychiatric condition, such as heart disease, diabetes, or depression — but that number dropped when people were first presented with various concerns for individuals and society.
Far fewer respondents approved the use of the technology to predict traits unrelated to disease, such as intelligence, height, and skin color.

The results suggest that educating people better about the current shortfalls and implications — including regulating the promises that companies can make — will temper optimism and help ensure that as these technologies develop, they will be implemented in scientifically sound, ethical, and equitable ways, the authors said.
How accurate are polygenic risk scores?
Up until now, patients undergoing IVF could choose which embryos to implant based on DNA tests that detect chromosomal abnormalities, such as Down syndrome, and diseases caused by mutations in a single gene, such as cystic fibrosis. Such screening, known as preimplantation genetic testing, is well-established and widely used.
By contrast, polygenic embryo screening estimates probabilities for conditions and traits influenced by many gene variants that each raise or lower risk by a small amount.
Experts disagree on how useful this technology might become in the future, but at present there are clear limitations to accuracy, Furrer said. Polygenic conditions arise from different combinations of genes, environment, and behaviors in ways that aren’t yet fully understood. The American College of Medical Genetics and Genomics has said that polygenic embryo screening is not yet suitable for clinical use.
This gap between the state of the science and the growing availability of such tests compelled Furrer and colleagues to conduct the survey. They hope the results inspire professionals to advocate for more informed dialogue and guidance around these technologies.

“The complexities and limitations of polygenic risk scores are challenging to convey.” Furrer said. “But we need to do so to ensure that people understand the high level of uncertainty that comes with estimating these risks.”
By the numbers
The survey drew from the team’s interviews with IVF patients and reproductive health specialists. Questions included lists of conditions, traits, and potential repercussions that participants were asked to weigh in on. The survey also made clear that polygenic risk scores could be used simply for information, to prepare for a future child, or to select an embryo for implantation.
The first part of the study surveyed more than 1,400 participants representing the wider U.S. population in age, gender, and race/ethnicity. It was conducted between March and July 2023.
Findings showed that: 72 percent of respondents approved of using polygenic embryo screening in general. 17 percent were ambivalent and 11 percent disapproved. 77 percent approved of selecting embryos based on risk of certain physical health conditions. 72 percent approved of selecting embryos based on risk of certain psychiatric health conditions. 36 percent approved of selecting embryos based on likelihood of certain behavioral traits. 30 percent approved of selecting embryos based on likelihood of certain physical traits. 92 percent expressed at least slight concern about polygenic embryo screening leading to false expectations about the future child. About half were “very” or “extremely” concerned about negative outcomes for individuals or society. 82 percent said they would be at least slightly interested in using polygenic embryo screening if they were already undergoing IVF. 30 percent said they would consider undergoing IVF to gain access to polygenic embryo screening.Approval was higher for using risk scores to prepare for a child than to select an embryo.
Positives and negatives
The second part of the study, conducted from March 2023 to February 2024 with about 200 respondents, placed the list of potential concerns at either the beginning or the end of the survey.
The concerns were: Parents having false expectations about the future child. Promoting eugenic thinking or practices — unethical efforts to select on a wide scale for traits considered desirable. Stigmatizing certain traits and conditions viewed as less desirable. Treating embryos like a product by selecting them based on preferred genetic chances for conditions or traits. Risk scores not being equally relevant for all ethnicities because of the Euro-centric nature of many genetic databases. Unequal access to the technology due to high cost. Low accuracy of genetic estimates for conditions or traits. Reduced diversity of human population. Possibility of nurtured genetics — parents consciously or unconsciously shaping their children’s environments based on the genetic estimates. Confusion over how to interpret and use test results. Guilt over decisions if the child develops a particular condition or trait. Discarding of embryos. Feeling pressured to use the technology.In the second survey, respondents given the list at the start reported lower overall approval (28 percentage points less) and more uncertainty (24 percentage points higher) about polygenic embryo screening than those who saw the list at the end — a finding that speaks to the importance of education and framing the public conversation.
How to find the right balance
Some of the survey results are nuanced, the authors note, and should not be taken as unqualified public support or rejection of polygenic embryo screening.
“These findings offer an initial glimpse into public opinion, predicated on a limited presentation of the technology,” said Furrer. “Future research must explore how opinions evolve.”
For instance, the team recommends further research into what it means that a majority of respondents approved of polygenic screening for selecting embryos but also expressed strong concerns about sliding into eugenics.
It will also be important to examine the role that personal and group values, such as reproductive freedom and autonomy, play in shaping public attitudes, the authors said.
The authors conclude that the work underscores the need to inform not only the public and IVF patients but also clinicians and genetic counselors, who need to be prepared to answer the rising tide of questions about the potential benefits, present limitations, and concerns surrounding polygenic embryo screening.
Authorship, funding, disclosures
Additional authors are Dorit Barlevy, Stacey Pereira, Shai Carmi, Todd Lencz, and principal investigator Gabriel Lázaro-Muñoz, assistant professor of psychiatry in the Center for Bioethics and Department of Global Health and Social Medicine at HMS.
This work was supported in part by the National Human Genome Research Institute at the National Institutes of Health (grant R01-HG011711). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.
All authors reported receiving NIH grants during the conduct of the study. Carmi also reported receiving personal fees from MyHeritage outside the submitted work.

Using an innovative new method, a University of Saskatchewan (USask) researcher is building tiny pseudo-organs from stem cells to help diagnose and treat Alzheimer’s.
When Dr. Tyler Wenzel (PhD) first came up with the idea of building a miniature brain from stem cells, he never could have predicted how well his creations would work.
Now, Wenzel’s “mini-brain” could revolutionize the way Alzheimer’s and other brain-related diseases are diagnosed and treated.
“Never in our wildest dreams did we think that our crazy idea would work,” he said. “These could be used as a diagnostic tool, built from blood.”
Wenzel, a postdoctoral fellow in the College of Medicine’s Department of Psychiatry, developed the idea for the “mini-brain” — or more formally, a one-of-a-kind cerebral organoid model — while working under the supervision of Dr. Darrell Mousseau (PhD).
Human stem cells can be manipulated to develop into practically any other cell in the body. Using stem cells taken from human blood, Wenzel was able to create a tiny artificial organ — roughly three millimetres across and resembling visually what Wenzel described as a piece of chewed gum someone has tried to smooth out again.
These “mini-brains” are built by creating stem cells from a blood sample, and then transforming these stem cells into functioning brain cells. Using small synthetic organoids for research is not a novel concept — but the “mini-brains” developed in Wenzel’s lab are unique. As outlined in Wenzel’s recent published article in Frontiers of Cellular Neuroscience, the brains from Wenzel’s lab are comprised of four different types of brain cells while most brain organoids are comprised of only neurons.

In testing, Wenzel’s “mini-brains” more accurately reflect a fully-fledged adult human brain, so they can be used to more closely examine neurological conditions of adult patients, such as Alzheimer disease.
And for those “mini-brains” created from the stem cells of individuals who have Alzheimer’s, Wenzel determined that the artificial organ displayed the pathology of Alzheimer’s — just on a smaller scale.
“If stem cells have the capacity to become any cell in the human body, the question then came ‘could we create something that resembles an entire organ?'” Wenzel said. “While we were developing it, I had the crazy idea that if these truly are human brains, if a patient had a disease like Alzheimer’s and we grew their ‘mini-brain,’ in theory that tiny brain would have Alzheimer’s.”
Wenzel said this technology has the potential to change the way health services are provided to those with Alzheimer’s, particularly in rural and remote communities. This groundbreaking research has already received support from the Alzheimer Society of Canada.
If Wenzel and his colleagues can create a consistent way to diagnose and treat neurological conditions like Alzheimer’s using only a small blood sample — which has a relatively long shelf life and can be couriered — instead of requiring patients to travel to hospitals or specialized clinics, it could be a tremendous resource savings for the healthcare system and a burden off of patients.
“In theory, if this tool works the way we think it does, we could just get a blood sample shipped from La Loche or La Ronge to the university and diagnose you like that,” he said.

The early proof-of-concept work on the “mini-brains” has been extremely promising — which means the next step for Wenzel is expanding the testing to a larger pool of patients.
The researchers are also interested in trying to expand the scope of the “mini-brain” research. According to Wenzel, if they can confirm the “mini-brains” accurately reflect other brain diseases or neurological conditions, they could potentially be used to speed up diagnoses or test the efficacy of drugs on patients.
As an example, Wenzel pointed to the substantial wait times to see a psychiatrist in Saskatchewan. If the “mini-brains” could be used to test which antidepressant works best on a patient suffering from depression, it could dramatically reduce the time required to see a doctor and receive a prescription.
A former high school science teacher who made the move into the world of research and academia, Wenzel said it’s the “nature of research” to come up with a hypothesis and hit close to the mark in an experiment that excites him his work.
The astounding success of the early “mini-brains,” however, has been so staggering that Wenzel admitted he still struggles to wrap his own brain around it.
“I’m still in disbelief, but it’s also extremely motivating that something like this happened,” Wenzel said. “It gives me something that I think will impact society and have actual relevance and create some change … it has a strong potential to shift the landscape of medicine.”

Though their states severely restrict abortion or place limits on having one through telehealth, about 8,000 women per month late last year were getting abortion pills by mail from states with legal protections for prescribers, a new survey finds.
Tuesday’s release of the #WeCount report is the first time a number has been put on how often the medical system workaround is being used. The research was conducted for the Society of Family Planning, which supports abortion rights.
The group found that by December 2023, providers in states with the protections were prescribing pills to about 6,000 women a month in states where abortion was banned at all stages of pregnancy or once cardiac activity can be detected — about 6 weeks, often before women realize they’re pregnant. The prescriptions also were going to about 2,000 women a month in states where the local laws limit abortion pill prescriptions by telemedicine.
“People … are using the various mechanisms to get pills that are out there,” Drexel University law professor David Cohen said. This “is not surprising based on what we know throughout human history and across the world: People will find a way to terminate pregnancies they don’t want.”
Medication abortions typically involve a combination two drugs: mifepristone and misoprostol. The rise of these pills, now used for most abortions in the U.S., is one reason total abortion numbers increased even after the Supreme Court overturned Roe v. Wade in 2022. The survey found that total monthly abortions hovered around 90,000 in 2023 — higher than the previous year.
After Roe was overturned, abortion bans took effect in most Republican-controlled states. Fourteen states now prohibit it with few exceptions, while three others bar it after about 6 weeks of pregnancy.
But many Democratic-controlled states went the opposite way. They’ve adopted laws intended to protect people in their states from investigations involving abortion-related crimes by authorities in other states. By the end of last year, five of those states — Colorado, Massachusetts, New York, Vermont, and Washington — had such protections in place specifically to cover abortion pill prescriptions by telemedicine.
“If a Colorado provider provides telehealth care to a patient who’s in Texas, Colorado will not participate in any Texas criminal action or civil lawsuit,” Cohen said. “Colorado says: ‘The care that was provided in our state was legal. It follows our laws because the provider was in our state.'”
Wendy Stark, president and CEO of Planned Parenthood of Greater New York, called the shield law there “a critical win for abortion access in our state.”
James Bopp Jr., general counsel for the National Right to Life Committee, said the law where the abortion takes place — not where the prescriber is located — should apply in pill-by-telemedicine abortions. That’s the way it is with other laws, he said.
But unlike many other aspects of abortion policy, this issue hasn’t been tested in court yet.
Bopp said that the only way to challenge a shield law in court would be for a prosecutor in a state with a ban to charge an out-of-state prescriber with providing an illegal abortion.
“It’ll probably occur, and we’ll get a legal challenge,” Bopp said.
Researchers note that before the shield laws took effect, people were obtaining abortion pills from sources outside the formal medical system, but it’s not clear exactly how many.
Alison Norris, MD, PhD, an epidemiologist at Ohio State University and a lead researcher on the #WeCount report, said the group is not breaking down how many pills were shipped to each state with a ban “to maintain the highest level of protection for individuals receiving that care and providers providing that care.”
Rebecca Gomperts, MD, PhD, director of Aid Access, an abortion pill supplier working with U.S. providers, said having more shield laws will make the healthcare system more resilient.
“They’re extremely important because they make doctors and providers … feel safe and protected,” said Gomperts, whose organization’s numbers were included in the #WeCount report. “I hope what we will see in the end is that all the states that are not banning abortion will adopt shield laws.”

Please enable JavaScript to view the comments powered by Disqus.

Claire Panosian Dunavan is a professor of medicine and infectious diseases at the David Geffen School of Medicine at UCLA and a past-president of the American Society of Tropical Medicine and Hygiene.

“What is my life?! Sometimes my life is so awful it’s surreal.” — March 2014 entry in the book Diary of a Dying Girl by Mallory Smith.
Daily battles with sticky secretions, steatorrhea, and constipation. Respiratory treatments, mucolytics, endless antibiotics. Sudden gushes of hemoptysis. A vibrant life repeatedly interrupted by ever-lengthening hospitalizations.
Then, in November 2017, everything ended 2 months after Mallory Smith received new lungs at the University of Pittsburgh, the only medical center in the country that would operate on a cystic fibrosis (CF) patient chronically colonized with Burkholderia cepacia.
Although some may find its name unfamiliar, today, this water- and soil-borne microbe is arguably the world’s worst superbug in a modern CF sufferer.
So, what actually killed Smith following her long-awaited transplant? A virulent, necrotizing pneumonia fueled not only by B. cepacia’s antimicrobial resistance (AMR) but its ability to trigger a massive release of inflammatory cytokines. As a final, desperate countermeasure, 24 hours before succumbing to “cepacia syndrome,” Smith even received special viruses called bacteriophage meant to destroy her invaders.
But, for Smith, the sci-fi weapons arrived too late.
And yet, what a luminous life she lived for 25 years, cherishing family and friends, attending and graduating from Stanford, surfing in Hawaii, savoring romance, and chronicling every step of her journey on her laptop.
Only after Smith died did Diane Shader Smith read her daughter’s intensely personal journal, then select excerpts that became Salt in My Soul, a posthumously published memoir. Then, just last week, Random House followed up with Diary of a Dying Girl so readers could take one more look at Smith’s short-but-extraordinary life.
Cystic Fibrosis, Then and Now
When considering the years that have passed since CF’s first description by Dorothy Andersen, MD, it’s hard to imagine another once-uniformly fatal genetic disease that has changed as much.
In the mid-1950s, affected infants often died before their first birthday, sometimes from malnutrition, sometimes from other complications stemming from faulty transport of chloride and water in their lungs, gut, and other organs. But by the 1980s and 1990s, CF youngsters were surviving far longer — so much so that many in their 20s and 30s were cycling in and out of adult hospital beds with fevers and thick globs of sputum that often grew highly resistant strains of Staph aureus or Pseudomonas aeruginosa.
Today, 56 years is the predicted life expectancy of a baby with CF born from 2018 through 2022, according to the Cystic Fibrosis Foundation. Moreover, half of all currently affected 3-year-olds are likely to live into their 60s.
What accounts for this remarkable shift?
In addition to antibiotics, nutritional strategies, and daily respiratory care, what tops the list are new, effective CF transmembrane conductance regulator (CFTR) modulator therapies designed to correct the malfunctioning protein made by the CFTR gene. The first of these new medications, ivacaftor (Kalydeco), was approved in 2012. Then came new combinations — tezacaftor-ivacaftor (Symdeko), lumacaftor-ivacaftor (Orkambi), and elexacaftor-tezacaftor-ivacaftor (Trikafta) — that expanded treatment to other genetic variants to reach a broader group of patients with CF.
The recent 80% drop in CF lung transplants in the U.S. is further proof of the modulators’ impact. Yet, despite their miraculous benefits, superbugs still pose deadly threats in the mucus-filled airways of advanced CF patients.
Superbug vs Superphage
In a moment we will segue to AMR writ large and the growing evidence that bacteriophage might soon eradicate certain deadly microbes in anyone from a CF sufferer to a war-wounded soldier to you or me. After all, there’s no guarantee any of us won’t someday acquire a dangerous drug-resistant pathogen.
But first, consider these thought-provoking facts about global AMR:Between 2000 and 2015, global antibiotic use increased by 65%In 2019, AMR contributed to roughly 5 million deaths worldwideWHO now includes AMR among its top 10 global health threats; without major interventions, AMR’s death toll will likely double by 2050One obvious battle-plan is to develop new antibiotics while curbing the excess antibiotic use that has long fueled AMR. That’s an ongoing global challenge.
But another hope for patients in truly desperate straits is to find and receive viruses that destroy superbugs. This strategy has recently caught fire thanks, in part, to the power of one man’s personal story.
I’m referring to The Perfect Predator, an electrifying book in which epidemiologist Steffanie Strathdee, PhD, describes how bacteriophages saved her husband’s life after he traveled to Egypt and developed gallstone pancreatitis and a football-sized pseudocyst awash in multi-drug resistant Acinetobacter baumannii. Tom Patterson, PhD, was initially medevaced to Germany, and then spent months septic and (often) comatose in the ICU at the University of California San Diego.
Meanwhile, Strathdee and her medical colleagues called multiple phage researchers until a viral match was found at Texas A&M, was approved for experimental use, then administered. Twenty-four hours later, Patterson emerged from the jaws of death.
Today, Strathdee (recognized as one of Time magazine’s 50 most influential people in healthcare in 2018) is the director of the Center for Innovative Phage Applications and Therapeutics (IPATH), the first dedicated phage therapy center in North America. In a recent paper, she highlighted a recent uptick in clinical trials of bacteriophage. And, according to her review of case reports published from 1999 through 2022, phage-based treatments have now been used to treat antibiotic-resistant infections involving skin, burn wounds, the prostate, the urinary tract, the abdomen, bones, heart valves, lungs, blood, and implanted devices.
Strathdee has made an impact outside of the research world too. At the request of Shader Smith, Strathdee authored the epilogue of Smith’s memoir, Salt in My Soul.
The Ongoing Fight Against AMR
It’s fair to say that Smith and Shader Smith are now known to almost everyone in the U.S.’s close-knit community of CF patients, family members, and healthcare professionals — Smith for her amazing grit and commitment to “living happy,” and Shader Smith for her passion to spur greater awareness of the global AMR threat.
One of many AMR-impacted CF patients Shader Smith has personally touched is a 25-year-old woman from Ohio with B. cepacia. Thanks to Shader Smith, Jennifer Nelson is currently receiving high-quality care at the University of Pittsburgh Medical Center and one day hopes to receive a lung transplant preceded by bacteriophage therapy.
Last month, I spoke with the former ballerina and competitive ice skater. All in all, Nelson said, her childhood was “pretty normal” until her teens, when her disease worsened and required more antibiotics, then took another downhill turn in her early 20s. Today, Nelson has 22,000 followers on Instagram, but she also has an ileostomy, requires parenteral nutrition, and sometimes uses oxygen for the simplest of physical tasks. Meanwhile, her B. cepacia isolate has become almost fully antibiotic-resistant.
Nonetheless, Nelson continues to believe that even in the worst situations, something good can emerge or lies hidden within.
“Having a mindset like that,” she continued, “when things are really awful, I’ve trained myself to think: what can this teach me? And then I search for that little 1% slice that could be positive.”
Shader Smith also continues to find higher purpose following Smith’s final battle. On May 7, 2024, she officially launched an initiative endorsed by CDC, WHO, and the European Centre for Disease Prevention and Control, among others, meant to raise awareness and shape new AMR policies through collective storytelling. For more, go to globalamrdiary.org.

Please enable JavaScript to view the comments powered by Disqus.

PARIS — Using a structured series of tests together, operators greatly improved the diagnostic accuracy of invasive coronary angiography (ICA) for people with chronic coronary syndrome (CCS), the prospective AID-ANGIO study showed.
Among people undergoing elective ICA, only 32.2% initially had their cause of myocardial ischemia identified as obstructive coronary artery disease based on that assessment alone.
With “advanced invasive diagnosis” (AID) — additional hierarchical assessment of intermediate-grade stenosis and functional coronary tests performed at the time of ICA — 84.2% had obstructive and/or non-obstructive mechanisms of ischemia confirmed (P

One in eight U.S. adults have taken semaglutide (Ozempic, Wegovy) or another GLP-1 agonist, a KFF poll found.
Metabolic benefits of semaglutide for weight loss were sustained for several years, according to findings presented at the European Congress on Obesity. In people with overweight or obesity without diabetes, semaglutide yielded an average 10.2% weight loss and 7.7 cm reduction in waist circumference after 4 years. (Nature Medicine)
Nearly 90% of U.S. adults 20 and older met any level criteria for “CKM syndrome” — a combination of cardiovascular, kidney, and metabolic risks — and 15% met criteria for advanced stages. (JAMA)
Around 25% of people 16 or older with insulin-dependent diabetes had eating disorder symptoms, according to a meta-analysis of 45 studies. (Eating Behaviors)
The Endocrine Society and European Society of Endocrinology released new joint guidelines on glucocorticoid-induced adrenal insufficiency. (Journal of Clinical Endocrinology & Metabolism)
An Australian study found people who were dispensed a GLP-1 receptor agonist were 44% more likely to also be dispensed an antidepressant. (Diabetes, Obesity and Metabolism)
Some women on GLP-1 receptor agonists are becoming pregnant after struggling with infertility. (CNN)
Hilary Cass, OBE, who published a report that led to restrictions on puberty blockers for transgender youth in Britain, said U.S. doctors are “out of date” on youth gender medicine. (New York Times)
Premature menopause was linked with early death in research presented at the annual European Congress of Endocrinology. (Newsweek)

Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Please enable JavaScript to view the comments powered by Disqus.

Rhode Island violated the civil rights of hundreds of children with mental health or developmental disabilities by routinely and unnecessarily segregating them at Bradley Hospital, an acute-care psychiatric hospital, federal prosecutors said Monday.
Zachary Cunha, U.S. Attorney for the District of Rhode Island, said the multi-year investigation found that — rather than complying with its legal obligation to provide services in the most integrated setting appropriate to the needs of the children — the state left them hospitalized at Bradley for months and in some cases for more than a year.
The findings have been sent to Gov. Dan McKee and the Rhode Island Department of Children, Youth, and Families.
“It is nothing short of appalling that the state has chosen to warehouse children in a psychiatric institution, rather than stepping up to provide the community care, support, and services that these kids need, and that the law requires,” Cunha said. He hopes the investigation will prompt the state to take swift action to meet its obligations under federal law.
The findings have been sent to Gov. Dan McKee and the Rhode Island Department of Children, Youth and Families (DCYF).
“This troubling report identifies long-standing issues where improvements are clearly needed,” said Olivia DaRocha, an aide to McKee, “issues that are exacerbated by the national shortage of home and community-based behavioral health services.”
“While the administration has taken actions to improve our current placement system, we understand that more must be done, and we support DCYF’s continued cooperation with the U.S. Attorney and the U.S. Department of Health and Human Services,” she added. “Together, we will continue to seek short- and long-term solutions to provide each child with a behavioral health disability the appropriate services in the most integrated setting.”
Although inpatient admissions at Bradley are designed to last only 1 to 2 weeks, the federal investigation concluded that children with behavioral health disabilities in DCYF’s care were often forced to languish in the hospital despite being ready for discharge, and despite the fact that the children would be better served in a family home, investigators said.
From Jan. 1, 2017, through Sept. 30, 2022, 527 children in the care or custody of DCYF — or receiving services voluntarily through the agency — were admitted to Bradley Hospital. Of these, 116 kids were hospitalized in a single admission for more than 100 consecutive days, 42 were hospitalized for more than 180 days, and seven were hospitalized for more than 1 year.
Many of the children were subjected to avoidable and unnecessarily lengthy hospitalizations because DCYF failed to provide the community-based services they need, according to investigators, who said keeping a child hospitalized for an extended period when their needs could be served in a less restrictive setting only exacerbates the child’s acute needs.
DCYF takes these findings very seriously, according to Damaris Teixeira, a public information officer for the department.
Starting in November 2022, the department has worked with Bradley Hospital and Hasbro Children’s Hospital to expedite discharges to appropriate placements as quickly as possible, he said. The state also launched a new Mobile Response and Stabilization Services program to provide time-limited, on-demand crisis intervention services in any setting in which a behavioral health crisis is occurring, including homes, schools, and emergency departments.
To date, 90% of the youth in the program did not end up requiring psychiatric hospitalization, he said.
The state is also investing about $45 million to expand in-state residential capacity, including a facility in Exeter that will serve 16 youth. The state Legislature also appropriated $11 million for the building of a 12-bed psychiatric residential facility to address in-state capacity need.
The investigation, which was also conducted by the HHS Office of Civil Rights, also found that DCYF’s failure to look for placements in a family home setting with services could lead both to delayed discharges and to inappropriate placements post-discharge, which, in turn, often leads to subsequent hospitalizations.
Office of Civil Rights Director Melanie Fontes Rainer said the investigation reinforces the agency’s commitment to continue to protect the right of individuals to live in their own homes and communities.
“We must do better by our children and the communities we serve, and states and others must follow federal civil rights laws to ensure every child can access care free from discrimination,” she said.

Please enable JavaScript to view the comments powered by Disqus.